Abstract
Adaptive immune responses are critical for protection against infection with Plasmodium parasites. The metabolic state dramatically changes in T cells during activation and the memory phase. Recent findings suggest that metformin, a medication for treating type-II diabetes, enhances T-cell immune responses by modulating lymphocyte metabolism. In this study, we investigated whether metformin could enhance anti-malaria immunity. Mice were infected with Plasmodium yoelii and administered metformin. Levels of parasitemia were reduced in treated mice compared with those in untreated mice, starting at ~2 weeks post-infection. The number of γδ T cells dramatically increased in the spleens of treated mice compared with that in untreated mice during the later phase of infection, while that of αβ T cells did not. The proportions of Vγ1+ and Vγ2+ γδ T cells increased, suggesting that activated cells were selectively expanded. However, these γδ T cells expressed inhibitory receptors and had severe defects in cytokine production, suggesting that they were in a state of exhaustion. Metformin was unable to rescue the cells from exhaustion at this stage. Depletion of γδ T cells with antibody treatment did not affect the reduction of parasitemia in metformin-treated mice, suggesting that the effect of metformin on the reduction of parasitemia was independent of γδ T cells.
| Original language | English |
|---|---|
| Number of pages | 1 |
| Journal | Frontiers in Immunology |
| Volume | 9 |
| DOIs | |
| Publication status | Published - Jan 1 2018 |
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Keywords
- clonal expansion
- malaria
- metabolism
- metformin
- protection
- γδ T cell
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion. / Miyakoda, Mana; Bayarsaikhan, Ganchimeg; Kimura, Daisuke; Akbari, Masoud; Udono, Heiichiro; Yui, Katsuyuki.
In: Frontiers in Immunology, Vol. 9, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion
AU - Miyakoda, Mana
AU - Bayarsaikhan, Ganchimeg
AU - Kimura, Daisuke
AU - Akbari, Masoud
AU - Udono, Heiichiro
AU - Yui, Katsuyuki
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Adaptive immune responses are critical for protection against infection with Plasmodium parasites. The metabolic state dramatically changes in T cells during activation and the memory phase. Recent findings suggest that metformin, a medication for treating type-II diabetes, enhances T-cell immune responses by modulating lymphocyte metabolism. In this study, we investigated whether metformin could enhance anti-malaria immunity. Mice were infected with Plasmodium yoelii and administered metformin. Levels of parasitemia were reduced in treated mice compared with those in untreated mice, starting at ~2 weeks post-infection. The number of γδ T cells dramatically increased in the spleens of treated mice compared with that in untreated mice during the later phase of infection, while that of αβ T cells did not. The proportions of Vγ1+ and Vγ2+ γδ T cells increased, suggesting that activated cells were selectively expanded. However, these γδ T cells expressed inhibitory receptors and had severe defects in cytokine production, suggesting that they were in a state of exhaustion. Metformin was unable to rescue the cells from exhaustion at this stage. Depletion of γδ T cells with antibody treatment did not affect the reduction of parasitemia in metformin-treated mice, suggesting that the effect of metformin on the reduction of parasitemia was independent of γδ T cells.
AB - Adaptive immune responses are critical for protection against infection with Plasmodium parasites. The metabolic state dramatically changes in T cells during activation and the memory phase. Recent findings suggest that metformin, a medication for treating type-II diabetes, enhances T-cell immune responses by modulating lymphocyte metabolism. In this study, we investigated whether metformin could enhance anti-malaria immunity. Mice were infected with Plasmodium yoelii and administered metformin. Levels of parasitemia were reduced in treated mice compared with those in untreated mice, starting at ~2 weeks post-infection. The number of γδ T cells dramatically increased in the spleens of treated mice compared with that in untreated mice during the later phase of infection, while that of αβ T cells did not. The proportions of Vγ1+ and Vγ2+ γδ T cells increased, suggesting that activated cells were selectively expanded. However, these γδ T cells expressed inhibitory receptors and had severe defects in cytokine production, suggesting that they were in a state of exhaustion. Metformin was unable to rescue the cells from exhaustion at this stage. Depletion of γδ T cells with antibody treatment did not affect the reduction of parasitemia in metformin-treated mice, suggesting that the effect of metformin on the reduction of parasitemia was independent of γδ T cells.
KW - clonal expansion
KW - malaria
KW - metabolism
KW - metformin
KW - protection
KW - γδ T cell
UR - http://www.scopus.com/inward/record.url?scp=85059926386&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059926386&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2018.02942
DO - 10.3389/fimmu.2018.02942
M3 - Article
C2 - 30619302
AN - SCOPUS:85059926386
VL - 9
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
ER -